Bacterial resistance to antibiotics: Modified target sites
Peter A. Lambert
Pharmaceutical and Biological Sciences, Aston University, Birmingham B4 7ET, United Kingdom
Received 22 November 2004; accepted 11 April 2005
Available online 16 June 2005
Abstract
Alteration in the target sites of antibiotics is a common mechanism of resistance. Examples of clinical strains showing
resistance can be found for every class of antibiotic, regardless of the mechanism of action. Target site changes often result from
spontaneous mutation of a bacterial gene on the chromosome and selection in the presence of the antibiotic. Examples include
mutations in RNA polymerase and DNA gyrase, resulting in resistance to the rifamycins and quinolones, respectively. In other
cases, acquisition of resistance may involve transfer of resistance genes from other organisms by some form of genetic
exchange (conjugation, transduction, or transformation). Examples of these mechanisms include acquisition of the mecA genes
encoding methicillin resistance in Staphylococcus aureus and the various van genes in enterococci encoding resistance to
glycopeptides.
D 2005 Elsevier B.V. All rights reserved.
Keywords: Bacterial resistance; Antibiotics; Modified targets; Resistance genes; Genetic exchange
Contents
1. Introduction ................................................... 1472
2. Penicillin binding proteins ........................................... 1472
2.1. MecA in MRSA ............................................. 1472
2.2. Mosaic PBPs in Streptococcus pneumoniae ............................... 1473
2.3. Altered PBPs in Neisseria gonorrhoeae ................................. 1473
2.4. Mosaic PBPs in Neisseria meningitidis ................................. 1474
2.5. Low affinity PBPs in enterococci .................................... 1474
2.6. h-Lactam resistance associated with PBP changes in other organisms ................. 1474
2.6.1. Haemophilus influenzae .................................... 1474
2.6.2. Helicobacter pylori ....................................... 1474
2.6.3. Proteus mirabilis, Acinetobacter baumanii and Pseudomonas aeruginosa ........... 1474
2.6.4. Streptococcus pyogenes..................................... 1474
2.6.5. Listeria monocytogenes ..................................... 1474
0169-409X/$ - see front matter D 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.addr.2005.04.003
E-mail address: p.a.lambert@aston.ac.uk.
Advanced Drug Delivery Reviews 57 (2005) 1471 – 1485
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